First-line therapy with palbociclib in patients with advanced HR+/HER2- breast cancer: The real-life study PALBOSPAIN.

PURPOSE: To evaluate the efficacy and safety of first-line therapy with palbociclib in a Spanish cohort treated after palbociclib approval. METHODS: PALBOSPAIN is an observational, retrospective, multicenter study evaluating real-world patterns and outcomes with 1 L palbociclib in men and women (any menopausal status) with advanced HR+/HER2- BC diagnosed between November 2017 and November 2019. The primary endpoint was real-world progression-free survival (rw-PFS). Secondary endpoints included overall survival (OS), the real-world response rate (rw-RR), the clinical benefit rate, palbociclib dose reduction, and safety. RESULTS: A total of 762 patients were included. The median rw-PFS and OS were 24 months (95% CI 21-27) and 42 months (40-not estimable [NE]) in the whole population, respectively. By cohort, the median rw-PFS and OS were as follows: 28 (95% CI 23-39) and 44 (95% CI 38-NE) months in patients with de novo metastatic disease, 13 (95% CI 11-17) and 36 months (95% CI 31-41) in patients who experienced relapse < 12 months after the end of ET, and 31 months (95% CI 26-37) and not reached (NR) in patients who experienced relapse > 12 months after the end of ET. rw-PFS and OS were longer in patients with oligometastasis and only one metastatic site and those with non-visceral disease. The most frequent hematologic toxicity was neutropenia (72%; grade ≥ 3: 52.5%), and the most common non-hematologic adverse event was asthenia (38%). CONCLUSION: These findings, consistent with those from clinical trials, support use of palbociclib plus ET as 1 L for advanced BC in the real-world setting, including pre-menopausal women and men. TRIAL REGISTRATION NUMBER: NCT04874025 (PALBOSPAIN). Date of registration: 04/30/2021 retrospectively registered.

[Recommendations for thromboembolic disease in oncological processes. A view from primary care]. / Recomendaciones sobre enfermedad tromboembólica venosa en procesos oncológicos. Una visión desde la medicina de familia.

Venous thromboembolic disease (VTE) is a frequent complication in patients diagnosed with cancer and a cause of morbidity and mortality. Approximately 20% of thromboembolic episodes develop in association with active cancer. On the other hand, it is estimated that about 2-12% of cases, the thromboembolic episode is the first manifestation of an occult cancer, diagnosed at that time or subsequently, which offers an opportunity for early diagnosis and treatment. There are multiple factors that contribute to increase the risk of VTE in oncological patients in relation to specific characteristics of the patient, the tumor and the treatments. Knowledge of these risk factors will contribute to early diagnosis when signs of VTE appear, as well as the assessment of thromboprophylaxis if indicated. The diagnosis of VTE in patients with cancer does not differ of those who do not suffer from it. Regarding the treatment of VTE in these patients, low molecular weight heparin (LMWH), direct acting anticoagulants (DACs) and antivitamin K (VKA) are the most commonly used, although the dosing regimen and length are not clear yet. The management of these patients should be interdisciplinary and early, so the primary care physician plays a key role in this process as he/she is liaise with his/her patients. It is also necessary to update knowledge in order to improve the care of these patients. For these reasons, this document has been prepared by the Working Group on Vasculopathies of the Spanish Society of Primary Care Physicians (SEMERGEN) whose objective is to present the available information regarding the management of VTE that may appear in oncological patients, as well as the assessment of thromboprophylaxis and treatment, if appropriate, from an approach focused on a primary care field.

Narrow pulse pressure is independently associated with massive transfusion and emergent surgery in hemodynamically stable trauma patients.

INTRODUCTION: Narrow pulse pressure (PP) is a sign of Class-II hemorrhage, but its clinical relevance is unknown. We hypothesized narrow PP is related to significant transfusion and need for emergent surgery. METHODS: Hemodynamically stable (SBP >/ = 90 mmHg) trauma patients were retrospectively reviewed. Narrow PP patients (<40 mmHg) were compared to normal patients (>/ = 40 mmHg). Outcomes included need for significant transfusion (>/ = 10 units) and emergent cavitary surgery. RESULTS: From 18,978 hemodynamically stable trauma patients admitted, 13% had narrow PP. They statistically required more massive transfusion, emergent surgery, or both (p < 0.0001), as well as higher mortality, longer hospital stay, and ICU stay (p < 0.0001). After controlling for age, gender, injury, ISS and GCS, NPP was independently associated with both significant transfusion and emergent surgery. CONCLUSION: In hemodynamically stable trauma patients, narrow PP is independently associated with three-fold increase in significant transfusion need and two-fold increase in emergent surgery need. Early identification of these patients may lead to more accurate and optimal intervention.

Observation of persistent species temperature separation in inertial confinement fusion mixtures.

The injection and mixing of contaminant mass into the fuel in inertial confinement fusion (ICF) implosions is a primary factor preventing ignition. ICF experiments have recently achieved an alpha-heating regime, in which fusion self-heating is the dominant source of yield, by reducing the susceptibility of implosions to instabilities that inject this mass. We report the results of unique separated reactants implosion experiments studying pre-mixed contaminant as well as detailed high-resolution three-dimensional simulations that are in good agreement with experiments. At conditions relevant to mixing regions in high-yield implosions, we observe persistent chunks of contaminant that do not achieve thermal equilibrium with the fuel throughout the burn phase. The assumption of thermal equilibrium is made in nearly all computational ICF modeling and methods used to infer levels of contaminant from experiments. We estimate that these methods may underestimate the amount of contaminant by a factor of two or more.

Late-Time Mixing Sensitivity to Initial Broadband Surface Roughness in High-Energy-Density Shear Layers.

Using a large volume high-energy-density fluid shear experiment (8.5 cm^{3}) at the National Ignition Facility, we have demonstrated for the first time the ability to significantly alter the evolution of a supersonic sheared mixing layer by controlling the initial conditions of that layer. By altering the initial surface roughness of the tracer foil, we demonstrate the ability to transition the shear mixing layer from a highly ordered system of coherent structures to a randomly ordered system with a faster growing mix layer, indicative of strong mixing in the layer at a temperature of several tens of electron volts and at near solid density. Simulations using a turbulent-mix model show good agreement with the experimental results and poor agreement without turbulent mix.

Queratoplastia endotelial con pelado de la Descemet asistida con láser de excímero en el síndrome iridocorneoendotelial / Excimer laser assisted Descemet stripping endothelial keratoplasty in iridocorneal endothelial syndrome

Caso clínico: Paciente femenina de 42 años con atrofia esencial de iris con disminución de la visión del ojo derecho, edema corneal moderado con pliegues en la membrana de Descemet, policoria, corectopia y atrofia iridiana. Se realizó queratoplastia endotelial con pelado de la Descemet asistida con láser de excímero obteniendo buena transparencia corneal y recuperación visual. Discusión: Los resultados al año, con agudeza visual de 0,4, conservación de la transparencia del cristalino, paquimetría de 588 μm y cilindro de 0,5 D, con baja pérdida endotelial alientan la realización de un estudio que valore la eficacia de la técnica en el síndrome iridocorneoendotelial (AU)

Case report: A 42 year-old female diagnosed with essential iris atrophy complained of visual decrease in the right eye. Examination revealed moderate corneal oedema, folds in Descemet's membrane, polycoria, corectopia, and iris atrophy.Excimer laser assisted Descemet stripping endothelial keratoplasty was performed, with a good corneal transparency and a significant visual improvement being obtained. Discussion: The results one year after the surgery, with visual acuity of 0.4, clear lens, pachymetry of 580 μm and cylinder of 0.5 D, with low endothelial cell loss, suggest that further studies are required to evaluate the efficacy of this technique in patients with iridocorneal endothelial syndrome (AU)

[Excimer laser assisted Descemet stripping endothelial keratoplasty in iridocorneal endothelial syndrome]. / Queratoplastia endotelial con pelado de la Descemet asistida con láser de excímero en el síndrome iridocorneoendotelial.

CASE REPORT: A 42 year-old female diagnosed with essential iris atrophy complained of visual decrease in the right eye. Examination revealed moderate corneal oedema, folds in Descemet's membrane, polycoria, corectopia, and iris atrophy. Excimer laser assisted Descemet stripping endothelial keratoplasty was performed, with a good corneal transparency and a significant visual improvement being obtained. DISCUSSION: The results one year after the surgery, with visual acuity of 0.4, clear lens, pachymetry of 580 µm and cylinder of 0.5 D, with low endothelial cell loss, suggest that further studies are required to evaluate the efficacy of this technique in patients with iridocorneal endothelial syndrome.

Determinación de vitaminas del Complejo B enArthrospira maxima por cromatografía líquidade alta resolución / The Determination of vitamin B-complex in Arthrospira maxima through high resolution liquid chromatography

Se diseñan dos métodos para la extracción de las vitaminas del complejo B en muestras de Arthrospira maxima cubana. Para la determinación, se emplea un sistema HPLC formado por una columna de octadecilsilano y fases móviles de metanol - agua - ácido fosfórico 0.1 mol/L (20:79.5:0.5) para el análisis de la cianocobalamina y (30:69.5:0.5) para el resto de las vitaminas, empleando hexanosulfonato sódico 5 mM en ambos casos. Las velocidades de flujo son de 1 y 0.8 mL/min respectivamente. La determinación se realiza a 362 y 270 nm. Se observó que la Arthrospira maxima cultivada en Cuba constituye una rica fuente de vitaminas del grupo B presentando un contenido promedio de 3.1 mg/10g de tiamina, 4.0 mg/10g de riboflavina, 9.0 mg/10g de piridoxina, 0.29 mg/10g de cianocobalamina, 21 mg/10g de ácido nicotínico y 26 mg/10g de nicotinamida (AU)

Visualization of the transport of primary and secondary bile acids across liver tissue in rats: in vivo study with fluorescent bile acids.

BACKGROUND/AIMS: Lysyl fluorescein conjugated bile acid analogues (LFCBAA) closely parallel their natural counterparts. To assess LFCBAA as a tool for the visualization of bile acid transport within liver tissue. METHODS: Wistar rats were administered physiological concentrations of the primary bile acid analogue cholyllysyl fluoroscein (CLF) and of the secondary bile acid analogue lithocholyllysyl fluorescein (LLF) and serial liver biopsies were taken at fixed intervals. Both compounds were also injected retrogradely into the biliary tree. Frozen sections were examined by fluorescence microscopy. RESULTS: Both CLF and LLF were rapidly taken up from sinusoidal blood but differed significantly in their hepatic handling. CLF was rapidly transported into bile, whereas LLF transport was slower and produced significantly more bile duct fluorescence. LLF clearance showed a lobular gradient with last remaining bile acid being confined largely to zone 3. Both compounds were avidly taken up by cholangiocytes after injection intravenously or retrogradely into the biliary tree. CONCLUSIONS: Visualization of LFCBAA by fluorescence microscopy may yield further information regarding hepatobiliary bile acid localization during studies of physiological and pathological mechanisms involved in transport of bile acids. The presence of both compounds within cholangiocytes strongly suggests that they may undergo a degree of chole-hepatic recirculation.

Plasma elimination of cholyl-lysyl-fluorescein (CLF): a pilot study in patients with liver cirrhosis.

BACKGROUND: Cholyl-lysyl-fluorescein (CLF) is a fluorescein-labelled bile acid whose biological behaviour closely resembles that of naturally occurring cholyl glycine. AIM: The aim of this study was to analyze the CLF plasma elimination in patients with liver cirrhosis. METHODS: A dose of CLF at 0.02 mg/kg b.w. was administered i.v. in 26 patients with liver cirrhosis and 9 healthy volunteers. Blood samples were collected before injection and then at 10 min intervals over 60 min. Plasma fluorescence was measured by a luminescence spectrometer and residual fluorescence over the time of the study was compared in each group. Routine liver function tests (rLFTs) were performed before each injection. RESULTS: Plasma elimination of CLF was significantly impaired in patients with cirrhosis compared to healthy subjects with p values <0.0001 at each analyzed time point. CLF test showed 100% sensitivity for liver cirrhosis when residual fluorescence was measured 30, 40, 50 and 60 min after injection. Routine LFTs showed 85% sensitivity for bilirubin, 84% for total bile acids, 69% for aspartate aminotransferase 62% for albumin and 50% for alkaline phosphatase. CLF elimination measured 60 min after injection correlated with Child-Pugh score (r=0.3945; p<0.05) and albumin (rs=0.6451; p<0.001). No adverse reaction or side effects of CLF were observed. CONCLUSIONS: CLF test clearly distinguished between the two analyzed groups and was more sensitive than routine liver function tests. The test appears safe, simple to perform and analyze and after validation in larger cohorts of patients may have the potential to become a useful dynamic test of liver function.

Recurrent autoimmune LKM hepatitis with multiple relapses.

We describe three females who since childhood and puberty have presented with several relapsing episodes of acute or chronic LKM positive hepatitis. Many episodes resolved spontaneously with recovery of normal liver function, although treatment with steroids, steroids/azathioprine was used at occasions. No clear pattern of precipitating factors has emerged though in some cases possible temporal relationship of episodes to menarche, oral contraceptives use or pregnancy has suggested a role for female sex hormones. We discuss briefly the possible mechanisms of LKM positive hepatitis, particularly in terms of drugs as possible trigger factors.

Cefixima para quimioprofilaxis antimeningocócica / Cefixime for antimeningococcal chemoprophylaxis

En una escuela pública, ubicada en un sector de Antofagasta con alta incidencia de enfermedad meningocócica, se tomaron muestras de secreción faríngea a 216 niños de 5 a 14 años de edad. Se encontraron 18 portadores de N. meningitidis grupo B (8,3 por ciento). Con el propósito de probar la eficacia de la cefixima para erradicar a esta bacteria en portadores sanos se administró a ellos cefixima en suspensión, 8 mgùkg de pesoùdía en una dosis diaria durante dos días. En 13/18 casos (72,2 por ciento) no se registraron reacciones adversas, los demás sufrieron reacciones leves que cedieron espontáneamente. Ningún cultivo faríngeo dio resultados positivos a los 7, 14 y 90 días después del tratamiento. A pesar de las limitaciones de nuestro estudio, la cefixima pudiese ser opción de alternativa eficaz para la quimioprofilaxis meningocócica

Pronóstico en niños con enfermedad meningocócica / Prognosis in children with meningoccocal disease

Entre el 1 de enero de 1987 y el 31 de diciembre de 1992 en forma retrospectiva y prospectivamente desde el 1 de enero de 1993 al 31 de julio de 1994, se reunieron antecedentes clínicos y de laboratorio de 67 niños que sufrieron enfermedad meningocócica en Antofagasta, con el propósito de probar el sistema de calificación de Stiehm y Damrosch y otros factores como predictores de la evolución de la enfermedad. Cada factor (púrpura de menos de 12 horas de evolución previo al ingreso; choque; ausencia de meningitis; menos de 10 000 glóbulos blancos por mm3 de sangre; VHS igual o menor a 1o mmHg, mostró asociación con mayor riesgo de fallecer y también el purpura fulminans y el compromiso de conciencia. La letalidad de la enfermedad fue mayor a 75 por ciento en los pacientes con tres o más de los cinco factores de riesgo del criterio de Stiehm y Damrosch. Se requieren estudios prospectivos y de análisis multivariados más completos para definir mejor las interrelaciones de los factores estudiados individualmente

Weight gain during pregnancy in adolescents: evaluation of a non-nutritional intervention.

The goal of the present work is to report the impact of psychological support, given during pregnancy to a group of adolescents, on maternal weight gain and their infants' birth weight. A total of 54 clinically healthy pregnant women of middle educational level were studied in Mexico City, beginning on the 20th week of pregnancy throughout the end of it. Before pregnancy there were no significant intergroup differences in height, age at menarche or expected weight for height; the groups were adolescents without psychological support (group I), adolescents with support (group II), and adults (group III). The median weight gains were 8.2, 11.0 and 12.2 kg for groups I, II and III respectively. Our results suggest that in favorable socioeconomic conditions, psychological support can be a non-nutritional intervention which can promote an adequate weight gain during pregnancy in adolescents, probably by diminishing their anxiety level.

PIP: A total of 54 healthy primiparous women with an uneventful full-term pregnancy were studied starting from the 20th week of pregnancy through the end of it at the Instituto Nacional de Perinatologia in Mexico City (INPer). They were divided into Group I (14 adolescents aged 15-18 years regularly attending the outpatient prenatal care clinic at INPer); Group II (18 adolescent women aged 14-18 years also attending the clinic but also receiving additional psychological support by a psychotherapy team); Group III (22 adult women aged 20-44 years who also were attending the clinic, but as Group I, did not receive psychological support). All women were studied at 20, 24, 30 and 34 weeks of pregnancy to establish the cumulative weight gain throughout pregnancy as well as their newborns' birth weight. All women were attended at monthly intervals in the prenatal care of the INPer. In terms of marital status, 53/54 of the women did have clear family support. Furthermore, 15/54 of the unmarried women also received emotional support from their partners. Group I, the adolescents lacking psychological support, had systematically lower weight gain than the other two groups, that is, Group I gained almost 3 kg less than the adolescents with support, and 4 kg less that the adult women. One quarter of the women of Group I did not gain any weight between weeks 20 and 24 and when their weight in the 20th week was compared to their pregestational weight, a weight loss of almost 1 kg was found. There were no differences in the infants' birth weight in the three groups (3.05, 2.95, and 3.00 kg for Groups I, II, and III). Systematic psychological support as a non-nutritional intervention throughout pregnancy can promote an adequate weight gain during pregnancy in adolescents aged 14 to 18 years, probably by diminishing their anxiety level and thus, their energy expenditure.

[A study of 10 cases of neonatal tetanus]. / Estudio de 10 casos de tetanos neonatal

PIP: Tetanus is an infectious disease that can occur at any age and is highly lethal. In the present study, a review was made of all cases of tetanus between January 1979 and June 1985 at the University Hospital "Dr. Eleuterio Gonzalez" in Monterrey, Nuevo Leon, Mexico. Out of a total of 76 cases, 10 were newborns. Of these, 5 were female and 5 male. The average age at admission was 8.5 days and the period of Collis was 32.3 hours. All had been born in a septic environment at term and with an average birthweight of 3120 kgs. Using Jandra's classification, 3 cases were considered mild, 5 moderate, and 2 severe. The laboratory tests were not relevant. 9 patients were given Phenobarbital and Diazepam as sedatives; 6 received total parenteral alimentation, and 5 newborns were given mechanical ventilation during an average of 26.6 days. The most common complications were respiratory problems and septicemia. The average length of hospitalization was 26.3 days with a mortality rate of 50%. (author's)^ieng